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A convenient route to enantiomerically pure, conjugated dienes from sugar allyltin derivatives
Tetrahedron: Asymmetry 11 (2000) 1997±2006
A convenient route to enantiomerically pure, conjugated dienes from sugar allyltin derivatives Sawomir Jarosz,* Stanislaw SkoÂra and Katarzyna Szewczyk Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, 01-224 Warsaw, Poland Received 20 March 2000; accepted 3 April 2000
Abstract The transformation of sugar allyltin derivatives into enantiomerically pure dienes (R*±CHCH± CHCH2) is presented. The internal double bond with the trans-con®guration is formed regardless of the con®guration of the starting sugar allyltin. # 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction The Diels±Alder reaction is one of the most important processes in the creation of carbon± carbon bonds.1 Application of chiral, enantiomerically pure dienes allows preparation of carbocyclic compounds in enantiomerically pure form. Simple monosaccharides are convenient starting materials for the preparation of such compounds, since most transformations of sugar molecules can be performed with high regio- and stereoselectivity. Many useful methods for the preparation of conjugated diene systems from sugars are reported in the literature.2 Recently, we elaborated a convenient method for the synthesis of such moleculesÐdienoaldehydes 2Ðfrom sugar allyltins3 1 (Fig. 1). Treatment of organometallic products 1 with a mild Lewis acid (e.g. zinc chloride) caused their conversion into the trans-dienes3 2Ðuseful synthons in the stereoselective preparation of enantiomerically pure bicyclo[4.3.0]nonene4 and bicyclo[4.4.0]decene5 derivatives (Fig. 1; 3 and 4, respectively). 2. Results and discussion The method of conversion of the allyltin derivatives into the diene system is based on a rearrangement±elimination procedure which requires the presence of an alkoxy function at the d * Corresponding author. E-mail: [email protected] 0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S0957-4166(00)00135-X
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Figure 1. Synthesis of chiral dienes from allyltin pyranosides and their application in synthesis
position. We have observed that this process aords the trans-dienes exclusively, regardless of the con®guration of starting allyltin derivative.6 Extension of this methodology for the preparation of other types of sugar-derived dienes is presented. 2.1. Synthesis of the dienes substituted with the furanose ring The preparation of chiral dienes substituted with a furanose ring consists of two steps: (i) transformation of a simple monosaccharide into the allyltin derivative; and (ii) treatment of the latter with a Lewis acid that should provide title compounds via a rearrangement±elimination sequence. The methodology is outlined in Scheme 1.
Scheme 1. (i) (COCl)2, DMSO, Et3N; (ii) Ph3PCHCO2Me; (iii) DIBAL-H; (iv) (a) NaH, THF, 30 min; (b) CS2, 30 min; (c) MeI, 2 h; (v) toluene, re¯ux, 3 h; (vi) Bu3SnH, AIBN, 110 C; (vii) ZnCl2, CH2Cl2, rt; (viii) Ph3PCHCHO; (ix) Ph3PCH2
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Thus, methyl 2,3,5-tri-O-benzyl-b-d-galactofuranoside7 (5) was converted into aldehyde 6 with the Swern reagent and further to a,b-unsaturated estery 7 by reaction with carbomethoxymethylenetriphenylphosphorane (Ph3PCH±CO2Me). Reduction of the ester function with DIBAL-H gave allylic alcohol 8, which was transformed into xanthate 9 by standard methodology. Thermal [3,3] rearrangement of the latter aorded thiocarbonate 10, which, upon reaction with tributyltin hydride, gave the desired organometallic product 11 as a single trans-isomer. As expected, the con®guration of the allyltin derivative (ca. 85:15 trans:cis) did not depend on the con®guration of the starting allylic alcohol (since the xanthate±thiocarbonate rearrangement: 90 !10 was not selective); however, treatment of the organometallic derivative with zinc chloride exclusively furnished the trans-diene 12 in good yield. Similarly, isomerically pure trans-diene 13 (d-xylo-con®gurated)8 was prepared from allyltin derivative 15, which was in turn prepared from the known 3,5-di-O-benzyl-1,2-O-isopropylidened-glucofuranose.9 2.2. Synthesis of the open-chain dienes from furanose derivatives Application of the methodology presented in Scheme 1 to derivatives of furanoses should result in similar transformations and provide dienes shorter by one carbon atom as compared to 2. Conversion of 3-O-benzyl-1,2-O-isopropylidene-5,6,7-trideoxy-7-tributylstannyl-oct-6-ene-a-d-ribo1,4-furanose3 17 and its d-xylo- analog 24 into such valuable synthons is presented in Scheme 2.
Scheme 2. (i) ZnCl2, CH2Cl2, rt; (ii) Et3N, C6H6, MeOH, H2O; (iii) Ph3PCHCO2Me; (iv) NaBH4; (v) NaIO4
Treatment of 17 with zinc chloride aorded hemiacetal 18; this product was relatively stable and its conversion into hydroxyaldehyde 19 was achieved by mild basic hydrolysis. Aldehyde 19 y
Con®guration of the double bond in such a,b-unsaturated esters is not important for the stereochemical outcome of the process leading to sugar allyltins. As we proved earlier (Ref. 3) the trans/cis mixture of the latter (with the sameÐ6:1Ð proportion of the trans:cis-isomers) is obtained regardless of the geometry of the double bond in the a,b-unsaturated ester.
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may serve as starting material for the preparation of a variety of dierently substituted chiral dienes with the E-con®guration of the internal double bond (assigned from the coupling constant J4,5 14.5 Hz, observed on the H-5 resonance at ca. 5.6 ppm). Reduction of the carbonyl group in 19 with sodium borohydride gave diol 20, whilst the Wittig reaction with a stabilized ylide aorded triene 21. Periodic cleavage of diol 20 followed by reduction of resulting aldehyde with NaBH4 provided alcohol 23 with only one stereogenic center. A similar reaction sequence performed on the d-xylo-organometallic analog 24, prepared from the corresponding allylic alcohol 2310 according to the methodology shown in Scheme 1, furnished dienes 25±29 in good yields. The con®guration at the stereogenic center in 29 was, of course, opposite to that in 22; thus, both enantiomers of this compound are available. The methodology presented in Scheme 2 allows for facile preparation of a-hydroxyaldehydes 19 and 26 or the diols derived from themÐdiols 20 and 28. However, it is not very useful for the simple preparation of fully protected dienoaldehydes, since the protection of the free hydroxy group in a-hydroxyaldehydes is troublesome. Application of other (fully protected) sugar stannanes may solve this problem (Scheme 3).
Scheme 3. (i) Swern oxidation; (ii) Ph3PCHCO2Me, CH2Cl2; (iii) (1) DIBAL-H; (2) NaH, THF, CS2, then MeI; (3) toluene, 110 C, 2 h; (4) Bu3SnH, AIBN, toluene, re¯ux; (iv) ZnCl2; (v) NaBH4
Methyl 2,3-di-O-benzyl-b-d-ribofuranoside11 30 was converted into unsaturated ester 31 as a ca. 4:1 mixture of E:Z-isomers and then into allyltin derivative 32 according to a method shown in Scheme 2. Treatment of the latter with a Lewis acid induced a rearrangement with elimination of tri-nbutyltin moiety and formation of the aldehyde 34, which was characterized further as alcohol 35. 3. Conclusion The synthesis of dierently substituted chiral, highly oxygenated dienes was realized by a mild Lewis acid induced, controlled decomposition of sugar allyltins. This procedure gives monosubstituted dienes with the trans-con®guration of the internal double bond exclusively. The convenient synthesis of unsaturated a-hydroxyaldehydes can also be realized by this methodology. 4. Experimental 4.1. General NMR spectra were recorded with a Varian Gemini 200 spectrometer for solutions in CDCl3 (internal Me4Si). Mass spectra [LSIMS (m-nitrobenzyl alcohol was used as a matrix to which
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sodium acetate was added) or EI] were recorded with an AMD-604 (AMD Intectra GmbH, Germany) mass spectrometer. Speci®c rotations were measured with a JASCO DIP Digital Polarimeter in chloroform solution (c 1) at room temperature. Column chromatography was performed on silica gel (Merck, 70±230 mesh). Organic solutions were dried over anhydrous magnesium or sodium sulfate. 4.2. Preparation of sugar allyltin derivatives The sugar allyltin derivatives were prepared from the corresponding alcohols 5, 14, and 30 according to our previously published methods3 involving (cf. Scheme 1): (i) (ii) (iii) (iv) (v) (vi)
oxidation of a sugar alcohol to an aldehyde; reaction with the stabilized Wittig reagent (to a,b-unsaturated ester); reduction of the ester function with DIBAL-H; formation of a xanthate; its thermal rearrangement into thiocarbonate; reaction with tri-n-butyltin hydride under radical conditions.
The procedure for the preparation of 11 is representative. 4.2.1. Methyl 2,3,5-tri-O-benzyl-6,7,8-trideoxy-8-tributylstannyl- -d-galacto-oct-6-eno-1,4-furanoside 11 To a solution of the Swern reagent12 (prepared from 1 mL of oxalyl chloride and 3 mL of DMSO in 30 mL of CH2Cl2) a solution of alcohol 57 (2.3 g, 5 mmol) in CH2Cl2 (15 mL) was added at ^78 C, and the mixture was stirred for 30 min at this temperature. Triethylamine (4 mL) was added, the mixture was stirred at ^78 C for another 30 min and partitioned between ether (100 mL) and water (30 mL). The organic layer was separated, washed with water, dried and concentrated, and the crude aldehyde 6 was dissolved in benzene (50 mL) containing Ph3PCHCO2Me (2.34 g, 7 mmol). After 16 h at room temperature, the solvent was evaporated in vacuum and the product ester 7 (trans:cis=2.5:1) was isolated by column chromatography (hexane:ethyl acetate, 6:1!3:1); yield 82%. trans-7: 1H NMR : 6.94 (dd, J5,6=5.7, J6,7=15.8, H-6), 6.09 (d, H-7), 4.95 (J1,2=0, H-1), 3.69 (CO2CH3), 3.35 (OCH3); 13C NMR : 166.2 (CO), 144.4 and 123.1 (C-6,7), 107.1 (C-1), 87.7, 82.7, 82.6 and 76.7 (C-2,3,4,5), 72.1, 71.7 and 71.6 (3CH2Ph), 54.9 and 51.6 (OCH3 and CO2CH3); HRMS m/z: 541.2202 [C31H34O7Na (M+Na+) requires 541.2202]. cis-7: 1H NMR : 6.35 (dd, J5,6=8.8, J6,7=11.7, H-6), 5.94 (dd, J5,7=0.87, H-7), 4.98 (d, J1,2=1.1, H-1), 3.67 (CO2CH3), 3.33 (OCH3); 13C NMR : 165.9 (CO), 146.9 and 121.9 (C-6,7), 107.2 (C-1), 87.9, 83.5 and 82.5 (C-2,3,4), 73.2, 72.0 and 71 (3CH2Ph), 54.9 and 51.4 (OCH3 and CO2CH3). To a cooled ^78 C solution of 7 (5 g, 9.7 mmol) in dry methylene chloride a 1 M solution of DIBAL-H in hexane (20 mL, 20 mmol) was added and the mixture was stirred for 2 h at ^78 C. The excess of hydride was decomposed by addition of ethyl acetate (2 mL) and, after warming to room temperature, water (10 mL). Insoluble material was ®ltered o by suction, the ®ltrate was dried, concentrated, and the productÐalcohol 8Ðwas isolated by column chromatography (hexane:ethyl acetate, 4:1!2:1); yield 86%. HRMS m/z: 513.2252 [C31H34O7Na (M+Na+) requires 513.2253].
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(Caution: The next sequence of reactions must be performed in a well-ventilated fume hood). To a solution of alcohol 8 (4.02 g, 8.2 mmol) in dry THF (30 mL) sodium hydride (ca. 60% suspension in mineral oil, 0.5 g) was added followed by a catalytic amount of imidazole (ca. 50 mg). The mixture was stirred at room temperature under an argon atmosphere for 1 h. Carbon disul®de (neat, 1 mL) was added and the mixture was stirred for another 30 min. MeI (1.5 mL) was then added, the mixture was stirred for 2 h at room temperature, and partitioned between ether (50 mL) and brine (20 mL). The organic layer was separated, washed with water, dried, and concentrated. A solution of crude xanthate 9 in dry toluene was purged with argon and heated under re¯ux until TLC (hexane:ethyl acetate, 5:1) indicated disappearance of the starting material and formation of a new slightly less polar product thiocarbonate 10 (2±3 h, two stereoisomers of very similar polarity were seen by TLC). Tri-n-butyltin hydride (2.9 mL, 11 mmol) in toluene (5 mL) was added dropwise over 5 min (caution: reaction is very exothermic), and heating was continued until TLC (hexane:ethyl acetate, 6:1) indicated disappearance of starting material and formation of a new less polar product (ca. 30 min). The solvent was evaporated under vacuum and the product was puri®ed by column chromatography (hexane:diethyl ether, 20:1!9:1) to aord 11 as colorless syrup, yield 53%. Compound 11 (pure trans-isomer). 1H NMR : 5.82 (ddd, J6,7=15.2, J7,8a=8.6, J7,8b=6.7, H-7), 5.34 (dd, J5,6=8.8, H-6), 4.96 (d, J1,2=1, H-1), 3.79 (dd, J4.5=3, H-4), 3.35 (OCH3); 13C NMR : 136.0 and 121.6 (C-6,7), 107.0 (C-1), 88.3, 84.0, 83.3 and 78.7 (C-2,3,4,5), 72.2, 71.7 and 69.4 (3CH2Ph), 54.7 (OCH3), 29.8, 27.3 and 9.9 [3Sn(CH2)3CH3], 14.5 (C-8), 13.7 [Sn(CH2)CH3]; HRMS m/z: 707.2743 [C38H51O120 5 Sn (M^57) requires 707.2759]. 4.2.2. 3,5-Di-O-benzyl-1,2-O-isopropylidene-6,7,8-trideoxy-8-tributylstannyl- -d-gluco-oct-6-eno-1,4furanose 15 This compound was prepared as a 9:1 trans:cis mixture from known 3,5-di-O-benzyl-1,2-Oisopropylidene-a-d-glucofuranose9 according to the above procedure. Overall yield: 45%. MS-EI m/z: [643, M^57]; 1H NMR for trans-15 : 5.98 (ddd, J6,7=15.2, J7,8a=8.0, J7,8b=5.9, H-7), 5.89 (d, J1,2=3.7, H-1), 5.29 (m, H-6), 1.83 (m, H-8a,b), 1.47 and 1.29 [C(CH3)2]; 13C NMR : 136.5 and 123.0 (C-6,7), 111.4 [C(CH3)2], 104.9 (H-1), 82.2, 81.9, 81.7 and 77.6 (C-2,3,4,5), 72.2 and 69.5 (2CH2Ph), 29.1, 27.3 and 13.7 [Sn(CH2)3CH3], 26.7 and 26.3 [C(CH3)2], 14.6 (C-8), 9.2 [Sn(CH2)3CH3]. 4.2.3. 3-O-Benzyl-1,2-O-isopropylidene-5,6,7-trideoxy-7-tributylstannyl- -d -xylo-hept-5-eno-1,4furanose 24 This compound was prepared as a ca. 4:1 mixture of trans:cis-isomers from known 3-O-benzyl1,2-O-isopropylidene-5,6-di-deoxy-a-d-xylo-hept-5(E/Z)-eno-1,4-furanose according to the procedure described in Section 4.2.1. 1 HRMS m/z: 523.1880 [C25H39O120 4 Sn (M^57) requires 523.1870]; H NMR data for the transisomer : 5.99 (m, H-6), 5.85 (d, J1,2=4.0, H-1), 5.45 (m, H-5), 3.71 (J2,3=0, J3,4=2.9, H-3), 1.50 and 1.30 [C(CH3)2]; 13C NMR : 136.9 and 118.2 (C-5,6), 111.0 [C(CH3)2], 104.4 (C-1), 83.9, 82.8 and 82.1 (C-2,3,4), 72.1 (CH2Ph), 29.1, 27.3 and 13.7 [3Sn(CH2)3CH3], 26.7 and 26.1, [C(CH3)2], 14.8 (C-7), 9.3 [Sn(CH2)3CH3]. 4.2.4. Methyl 2,3-di-O-benzyl-5,6,7-trideoxy-7-tributylstannyl- -d-ribo-hept-5-eno-1,4-furanoside 32 This compound was prepared from known11 alcohol 30, via unsaturated ester 31 {ca. 4:1 trans:cis mixture. HRMS m/z: 421.1625 [C23H26O6Na (M+Na+) requires 421.1627]; data for the
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main trans-isomer: 1H NMR : 6.94 (dd, J4,5=5.5, J5,6=15.8, H-5), 6.10 (dd, J4,6=1.5, H-6), 4.92 (J1,2=0, H-1), 3.74 (CO2CH3), 3.36 (OCH3); 13C NMR : 146.6 and 121.2 (CO), 106.4 (C-1), 81.8, 79.8 and 79.5 (C-2,3,4), 72.8 and 72.4 (2CH2Ph), 55.6 and 51.6 (OCH3 and CO2CH3)} according to the procedure described in Section 4.2.1. Compound 32 (only trans). 1H NMR : 5.92 (ddd, J5,6=14.9, J6,7a=8.8, J6,7b=8.5, H-6), 5.21 (dd, J4,5=8.3, H-5), 4.86 (J1,2=0, H-1), 3.34 (OCH3); 13C NMR : 135.2 and 124.4 (C-5,6), 105.6 (C-1), 82.8, 82.3 and 80.1 (C-2,3,4), 72.5 and 72.2 (2CH2Ph), 54.9 (OCH3), 29.1, 27.3 and 9.2 [Sn(CH2)3CH3], 14.6 (C-7), 13.8 [Sn(CH2)3CH3]; HRMS m/z: 667.2789 [C34H52O4Na120Sn (M+Na+) requires 667.2785]. 4.3. Reaction of sugar allyltin derivatives with Lewis acids The corresponding allyltin derivative (11, 15, 17, 24 or 32; 3 mmol each) was dissolved in anhydrous methylene chloride (30 mL). A 2.0 M solution of ZnCl2 etherate in methylene chloride (3 mL, 6 mmol) was added, the mixture was stirred at room temperature for 20 min, and partitioned between ether (50 mL) and brine (30 mL). The organic layer was separated, washed with water, dried and concentrated and the products were isolated by column chromatography (hexane:diethyl ether, 7:1). Dienes 18 and 25 were characterized as acetates. 4.3.1. Methyl 2,3-di-O-benzyl-5,6,7,8-tetradeoxy- -l-arabino-oct-5(E),7-dieno-1,4-furanoside 12 1 H NMR : 6.33 (m, H-6,7), 5.72 (dd, J4,5=7.8, J5,6=14.1, H-5), 5.19 (m, both H-8), 4.91 (d, J1,2=1.3, H-1), 4.44 (m, J3,4=7.1, H-4), 4.00 (dd, J2,3=3.5, H-2), 3.78 (dd, H-3), 3.37 (OCH3); 13 C NMR : 136.0, 133.8 and 130.8 (C-5,6,7), 118.4 (C-8), 88.6, 87.5 and 81.3 (C-2,3,4), 72.3 and 72.0 (2CH2Ph), 54.8 (OCH3); HRMS m/z: 389.1752 [C23H26O4Na (M+Na+) requires 389.1729]. 4.3.2. 3-O-Benzyl-1,2-O-isopropylidene-5,6,7,8-tetradeoxy- -d-xylo-oct-5(E),7-dieno-1,4-furanose8 13 When this compound was prepared by controlled decomposition of allyltin 15 only the transisomer was detected in the NMR spectra. 1 H NMR : 6.36 (m, H-6,7), 5.95 (d, J1,2=3.8, H-1), 5.85 (dd, J4,5=7.5, J5,6=14.8, H-5), 5.20 (m, both H-8), 3.85 (dd, J3,4=3.1, H-3), 1.50 and 1.31 [C(CH3)2]; 13C NMR : 136.1, 134.6, 127.1 (C-5,6,7), 118.2 (C-8), 111.4 [C(CH3)2], 104.7 (C-1), 83.4, 82.9, 80.8 (C-2,3,4), 72.0 (CH2Ph), 26.7, 26.1 [C(CH3)2]. When this product was obtained according to Narkunan and Nagarajan8 (see also Scheme 1) additional signals, that could be connected with the cis-isomer, were seen in the 13C NMR spectrum at : 133.0, 131.7, 125.0 (C-5,6,7), 119.8 (C-8), and 112.1 [C(CH3)2]. Also, in the 1H NMR spectrum the H-3 resonance split into two signals at : 3.89 (the minor cis-isomer) and 3.85 (the main trans-isomer). Integration of these signals allowed us to estimate the trans:cis ratio at 9:1. 4.3.3. 1-O-Acetyl-3-O-benzyl-1,2-O-isopropylidene-4,5,6,7-tetradeoxy-4(E),6-dieno-d-erythro-heptose 18-Ac 1 H NMR : 6.36 (m, H-5,6), 6.22 (d, J1,2=2.3, H-1), 5.65 (dd, J3,4=7.7, J4,5=14.5, H-4), 5.21 (m, H-7), 4.23 (dd, J2,3=6.2, H-2), 3.87 (dd, H-3), 2.07 (COCH3), 1.47 and 1.46 [C(CH3)2]; 13C NMR : 170.1 (CO), 135.9, 135.8 and 129.0 (C-4,5,6), 118.7 (C-7), 112.9 [C(CH3)2], 96.6 (C-1), 83.6 and 78.8 (C-2,3), 70.5 (CH2Ph), 27.2 and 26.7 [C(CH3)2], 21.2 (COCH3).
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4.3.4. 1-O-Acetyl-3-O-benzyl-1,2-O-isopropylidene-4,5,6,7-tetradeoxy-4(E),6-dieno-d-threo-heptose 25-Ac 1 H NMR : 6.34 (m, H-5,6), 6.17 (d, J1,2=2.3, H-1), 5.63 (dd, J3,4=8.2, J4,5=14.6, H-4), 5.20 (m, both H-7), 4.30 (dd, J2,3=5.5, H-2), 3.95 (dd, H-3), 2.06 (COCH3), 1.48 and 1.44 [C(CH3)2]; 13 C NMR : 170.2 (CO), 136.2, 135.5 and 128.7 (C-4,5,6), 118.9 (C-7), 113.1 [C(CH3)2], 96.4 (C-1), 83.8 and 78.3 (C-2,3), 70.2 (CH2Ph), 27.0 and 26.9 [C(CH3)2], 21.2 (COCH3); HRMS m/z: 355.1521 [C19H24O5Na (M+Na+) requires 355.1521]. 4.4. Basic hydrolysis of dioxolanes 18 and 25 To a solution of 18 or 25 (3 mmol) in benzene (30 mL), triethylamine (1 mL), methanol (1 mL) and water (1 mL) were added and the mixture was stirred at room temperature for 3 h. Toluene (20 mL) was added, and the solution was concentrated to ca. half volume, dried and concentrated to give in almost quantitative yield 2(R)-hydroxy-3(R)-benzyloxy-hepta-4(E),6-dienal 19 and 2(R)hydroxy-3(S)-benzyloxy-hepta-4(E),6-dienal 26. These hydroxyaldehydes were rather unstable and should be prepared directly before use in the next step. 4.5. Reaction of hydroxyaldehydes with the stabilized Wittig reagent Freshly prepared aldehyde (19 or 26; 1 mmol) was dissolved in dry benzene (10 mL) to which Ph3PCH±CO2Me (0.5 g, 1.5 mmol) was added. The mixture was stirred for 3 h at room temperature, concentrated, and the product was isolated by column chromatography (hexane:ethyl acetate, 6:1). 4.5.1. Methyl 4(R)-hydroxy-5(R)-benzyloxy-nona-2(E),6(E),8-trienoate 21 [ ]D ^87.7. 1H NMR : 6.95 (dd, J2,3=15.8, J3,4=4.6, H-3), 6.33 (m, H-7,8), 6.11 (dd, J2,4=1.7, H-2), 5.62 (dd, J5,6=8.1, J6,7=14.5, H-6), 5.22 (m, both H-9), 4.36 (H-4), 3.93 (dd, J4,5=4.4, H-5), 3.72 (CO2CH3); 13C NMR : 166.7 (CO), 145.7 and 121.6 (C-2,3), 136.2, 135.7 and 128.7 (C-6,7,8), 118.9 (C-9), 81.6 (C-5), 72.9 (C-4), 70.4 (CH2Ph), 51.5 (CO2CH3); HRMS m/z: 311.1280 [C17H20O4Na (M+Na+) requires 311.1259]. 4.5.2. Methyl 4(R)-hydroxy-5(S)-benzyloxy-nona-2(E),6(E),8-trienoate 27 [ ]D +116.0. 1H NMR : 6.89 (dd, J2,3=15.6, J3,4=4.2, H-3), 6.36 (m, H-7,8), 6.16 (dd, J2,4=1.9, H-2), 5.61 (dd, J5,6=8.4, J6,7=14.3, H-6), 5.24 (m, both H-9), 4.27 (m, H-4), 3.73 (H-5, CO2CH3); 13C NMR : 166.7 (CO), 145.6 and 121.6 (C-2,3), 136.6, 135.6 and 128.8 (C-6,7,8), 119.3 (C-9), 82.2 (C-5), 73.1 (C-4), 70.4 (CH2Ph), 51.6 (CO2CH3); HRMS m/z: 311.1289 [C17H20O4Na (M+Na+) requires 311.1259]. 4.6. Reduction of hydroxyaldehydes 19, 26 and alkoxyaldehyde 34 Freshly prepared aldehyde 19 or 26 (1 mmol; obtained by hydrolysis of the corresponding dioxolanes, 18 and 25) or 34 (obtained by the controlled decomposition of 1 mmol of allyltin 32 according to Section 4.3) was dissolved in a THF:methanol mixture (1:1 v/v, 20 mL), to which sodium borohydride (0.1 g) was added. The mixture was stirred for 1 h, concentrated, then the product was extracted with ether, acetylated under standard conditions and puri®ed by column chromatography (hexane:ethyl acetate, 2:1).
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4.6.1. 1,2(R)-Di-acetoxy-3(R)-benzyloxy-hepta-4(E),6-diene 20-Ac [ ]D ^88.9. 1H NMR : 6.33 (m, H-5,6), 5.60 (dd, J3,4=8.1, J4,5=14.3, H-4), 5.20 (m, H-2, both H-7), 3.96 (dd, J2,3=6.2, H-3), 2.01 and 1.99 (2COCH3); 13C NMR : 170.5 and 170.0 (2CO), 135.7, 135.6 and 129.3 (C-4,5,6), 118.7 (C-7), 77.6 and 72.4 (C-2,3), 70.3 (CH2Ph), 62.4 (C-1), 20.8 and 20.7 (2COCH3); HRMS m/z: 341.1362 [C18H22O5Na (M+Na+) requires 341.1365]. 4.6.2. 1,2(R)-Di-acetoxy-3(S)-benzyloxy-hepta-4(E),6-diene 28-Ac [ ]D +26.6. 1H NMR : 6.34 (m, H-5,6), 5.59 (dd, J3,4=7.8, J4,5=14.5, H-4), 5.22 (m, H-2, both H-7), 4.31 and 4.10 (2dd, J1a,1b=11.8, J1a,2=3.7, J1b,2=7.0, both H-1), 4.01 (dd, J2,3=5.3, H-3), 2.08 and 1.99 (2COCH3); 13C NMR : 170.5 and 170.2 (2CO), 135.7, 135.5 and 128 (C-4,5,6), 118.9 (C-7), 77.2 and 72.5 (C-2,3), 70.4 (CH2Ph), 62.8 (C-1), 20.9 and 20.7 (2COCH3); HRMS m/z: 341.1350 [C18H22O5Na (M+Na+) requires 341.1365]. 4.6.3. 1-Acetoxy-2(R),3(S)-di-benzyloxy-hepta-4(E),6-diene 35-Ac 1 H NMR : 6.35 (m, H-5,6), 5.68 (dd, J3,4=8.1, J4,5=14.5, H-4), 5.21 (m, both H-7), 4.32 (dd, J1a,1b=11.8, J1a,2=3.7, H-1a), 4.19 (dd, J1b,2=5.7, H-1b), 3.95 (dd, J2,3=5.7, H-3), 3.68 (m, H-2), 1.98 (COCH3); 13C NMR : 170.8 (CO), 136.0, 135.2 and 130.6 (C-4,5,6), 118.1 (C-7), 79.0 and 78.8 (C-2,3), 72.8 and 70.4 (2CH2Ph), 63.4 (C-1), 20.9 (COCH3); HRMS m/z: 389.1725 [C23H26O4Na (M+Na+) requires 389.1729]. 4.7. Synthesis of dienes 22 and 29 Diol 20 or 28 (1 mmol) was dissolved in ether (20 mL) and added to a solution of sodium periodate (0.7 g) in water (10 mL). The heterogeneous mixture was stirred for 30 min, the organic layer was separated, dried and concentrated, and the crude aldehyde was reduced with sodium borohydride as described in Section 4.6. For better characterization, products alcohols 22 and 29 were acetylated and these derivatives were puri®ed by column chromatography (hexane:ethyl acetate, 4:1) 4.7.1. 1-Acetoxy-2(R)-benzyloxy-hexa-3(E),5-diene 22-Ac [ ]D ^87.9. 1H NMR : 6.35 (m, H-4,5), 5.61 (dd, J2,3=6.8, J3,4=14.3, H-3), 5.19 (m, both H6), 4.11 (m, H-2, both H-1), 2.05 (COCH3); 13C NMR : 170.8 (CO), 135.8, 134.8 and 129.6 (C3,4,4), 118.6 (C-6), 76.9 (C-2), 70.4 (CH2Ph), 66.2 (C-1), 20.8 (COCH3); HRMS m/z: 269.1165 [C15H18O3Na (M+Na+) requires 269.1154]. 4.7.2. 1-Acetoxy-2(S)-benzyloxy-hexa-3(E),5-diene 29-Ac (=ent-22-Ac) [ ]D +85.5. HRMS m/z: 269.1153 [C15H18O3Na (M+Na+) requires 269.1154]. The NMR spectra of this compound were identical in all respects with the spectra of 22-Ac. References 1. Pindur, U.; Lutz, G.; Otto, Ch. Chem. Rev. 1993, 93, 741±761. 2. See, for example: Guliano, R. M.; Buzby, J. H.; Marcopulos, M.; Dpringor, J. P. J. Org. Chem. 1990, 55, 3555± 3562, and references cited therein; Lopez, J. C., Lameignere, E.; Burnouf, C.; Laborde, M. A.; Ghini, A. A.; Olesker, A.; Lukacs, G. Tetrahedron 1993, 49, 7701±7722; Gomez, A. M.; Lopez, J. C.; Fraser-Reid, B. Synthesis
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3. 4. 5. 6. 7. 8.
9. 10. 11. 12.
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1993, 943±944; Lopez, J. C.; Gomez, A. M.; Fraser-Reid, B. J. Chem. Soc., Chem. Commun. 1993, 762±764; Roman, E.; Banos, M.; Higes, F. J.; Serrano, J. A. Tetrahedron: Asymmetry 1998, 9, 449±458, and references cited therein. Kozowska, E.; Jarosz, S. Carbohydr. Res. 1994, 13, 889±898. . Jarosz, S.; Kozowska, E.; Jezewski, A. Tetrahedron 1997, 53, 10 775±10 282; Jarosz, S.; SkoÂra, S. Tetrahedron: Asymmetry 2000, 11, 1425±1432. Jarosz, S. J. Chem. Soc., Perkin Trans. 1 1997, 3579±3580; Jarosz, S.; SkoÂra, S. Tetrahedron: Asymmetry 2000, 11, 1433±1448. Ref. 3; see also Jarosz, S. Tetrahedron 1997, 53, 10 765±10 774. Veeneman, G. H.; Notermans, S.; Hoogerhout, P.; van Boom, J. H. Recl. Trav. Chim. Pays-Bass 1989, 108, 344± 350. This compound was prepared previously from aldehyde 16 by a two-step procedure involving: (i) reaction with Ph3PCH±CHO; and next with (ii) Ph3PCH2 (Narkunan, K.; Nagarajan, M. J. Chem. Soc., Chem. Commun. 1994, 1705±1706). Although this sequence was reported to be highly selective, we obtained a 9:1 mixture of the trans:cis-isomers because of the lack of selectivity in the ®rst step. Eby, R.; Schuerch, C. Carbohydr. Res. 1982, 100, c41±c43; Stepowska, H.; Zamojski, A. Carbohydr. Res. 1994, 265, 133±138. Brimacombe, J. S.; Kabir, A. K. M. S. Carbohydr. Res. 1986, 150, 35±51; Kawahata, Y.; Takatsuto, S.; Ikekawa, N.; Murat, M.; Omura, S. Chem. Pharm. Bull. 1986, 34, 3102±3110. Mereyala, H. B.; Gurrala, S. R. Chem. Lett. 1998, 863±864. Mancuso, A. J.; Huang, S.-L.; Swern, D. J. Org. Chem. 1978, 43, 2480±2482.
A convenient route to enantiomerically pure, conjugated dienes from sugar allyltin derivatives Sawomir Jarosz,* Stanislaw SkoÂra and Katarzyna Szewczyk Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, 01-224 Warsaw, Poland Received 20 March 2000; accepted 3 April 2000
Abstract The transformation of sugar allyltin derivatives into enantiomerically pure dienes (R*±CHCH± CHCH2) is presented. The internal double bond with the trans-con®guration is formed regardless of the con®guration of the starting sugar allyltin. # 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction The Diels±Alder reaction is one of the most important processes in the creation of carbon± carbon bonds.1 Application of chiral, enantiomerically pure dienes allows preparation of carbocyclic compounds in enantiomerically pure form. Simple monosaccharides are convenient starting materials for the preparation of such compounds, since most transformations of sugar molecules can be performed with high regio- and stereoselectivity. Many useful methods for the preparation of conjugated diene systems from sugars are reported in the literature.2 Recently, we elaborated a convenient method for the synthesis of such moleculesÐdienoaldehydes 2Ðfrom sugar allyltins3 1 (Fig. 1). Treatment of organometallic products 1 with a mild Lewis acid (e.g. zinc chloride) caused their conversion into the trans-dienes3 2Ðuseful synthons in the stereoselective preparation of enantiomerically pure bicyclo[4.3.0]nonene4 and bicyclo[4.4.0]decene5 derivatives (Fig. 1; 3 and 4, respectively). 2. Results and discussion The method of conversion of the allyltin derivatives into the diene system is based on a rearrangement±elimination procedure which requires the presence of an alkoxy function at the d * Corresponding author. E-mail: [email protected] 0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S0957-4166(00)00135-X
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Figure 1. Synthesis of chiral dienes from allyltin pyranosides and their application in synthesis
position. We have observed that this process aords the trans-dienes exclusively, regardless of the con®guration of starting allyltin derivative.6 Extension of this methodology for the preparation of other types of sugar-derived dienes is presented. 2.1. Synthesis of the dienes substituted with the furanose ring The preparation of chiral dienes substituted with a furanose ring consists of two steps: (i) transformation of a simple monosaccharide into the allyltin derivative; and (ii) treatment of the latter with a Lewis acid that should provide title compounds via a rearrangement±elimination sequence. The methodology is outlined in Scheme 1.
Scheme 1. (i) (COCl)2, DMSO, Et3N; (ii) Ph3PCHCO2Me; (iii) DIBAL-H; (iv) (a) NaH, THF, 30 min; (b) CS2, 30 min; (c) MeI, 2 h; (v) toluene, re¯ux, 3 h; (vi) Bu3SnH, AIBN, 110 C; (vii) ZnCl2, CH2Cl2, rt; (viii) Ph3PCHCHO; (ix) Ph3PCH2
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Thus, methyl 2,3,5-tri-O-benzyl-b-d-galactofuranoside7 (5) was converted into aldehyde 6 with the Swern reagent and further to a,b-unsaturated estery 7 by reaction with carbomethoxymethylenetriphenylphosphorane (Ph3PCH±CO2Me). Reduction of the ester function with DIBAL-H gave allylic alcohol 8, which was transformed into xanthate 9 by standard methodology. Thermal [3,3] rearrangement of the latter aorded thiocarbonate 10, which, upon reaction with tributyltin hydride, gave the desired organometallic product 11 as a single trans-isomer. As expected, the con®guration of the allyltin derivative (ca. 85:15 trans:cis) did not depend on the con®guration of the starting allylic alcohol (since the xanthate±thiocarbonate rearrangement: 90 !10 was not selective); however, treatment of the organometallic derivative with zinc chloride exclusively furnished the trans-diene 12 in good yield. Similarly, isomerically pure trans-diene 13 (d-xylo-con®gurated)8 was prepared from allyltin derivative 15, which was in turn prepared from the known 3,5-di-O-benzyl-1,2-O-isopropylidened-glucofuranose.9 2.2. Synthesis of the open-chain dienes from furanose derivatives Application of the methodology presented in Scheme 1 to derivatives of furanoses should result in similar transformations and provide dienes shorter by one carbon atom as compared to 2. Conversion of 3-O-benzyl-1,2-O-isopropylidene-5,6,7-trideoxy-7-tributylstannyl-oct-6-ene-a-d-ribo1,4-furanose3 17 and its d-xylo- analog 24 into such valuable synthons is presented in Scheme 2.
Scheme 2. (i) ZnCl2, CH2Cl2, rt; (ii) Et3N, C6H6, MeOH, H2O; (iii) Ph3PCHCO2Me; (iv) NaBH4; (v) NaIO4
Treatment of 17 with zinc chloride aorded hemiacetal 18; this product was relatively stable and its conversion into hydroxyaldehyde 19 was achieved by mild basic hydrolysis. Aldehyde 19 y
Con®guration of the double bond in such a,b-unsaturated esters is not important for the stereochemical outcome of the process leading to sugar allyltins. As we proved earlier (Ref. 3) the trans/cis mixture of the latter (with the sameÐ6:1Ð proportion of the trans:cis-isomers) is obtained regardless of the geometry of the double bond in the a,b-unsaturated ester.
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may serve as starting material for the preparation of a variety of dierently substituted chiral dienes with the E-con®guration of the internal double bond (assigned from the coupling constant J4,5 14.5 Hz, observed on the H-5 resonance at ca. 5.6 ppm). Reduction of the carbonyl group in 19 with sodium borohydride gave diol 20, whilst the Wittig reaction with a stabilized ylide aorded triene 21. Periodic cleavage of diol 20 followed by reduction of resulting aldehyde with NaBH4 provided alcohol 23 with only one stereogenic center. A similar reaction sequence performed on the d-xylo-organometallic analog 24, prepared from the corresponding allylic alcohol 2310 according to the methodology shown in Scheme 1, furnished dienes 25±29 in good yields. The con®guration at the stereogenic center in 29 was, of course, opposite to that in 22; thus, both enantiomers of this compound are available. The methodology presented in Scheme 2 allows for facile preparation of a-hydroxyaldehydes 19 and 26 or the diols derived from themÐdiols 20 and 28. However, it is not very useful for the simple preparation of fully protected dienoaldehydes, since the protection of the free hydroxy group in a-hydroxyaldehydes is troublesome. Application of other (fully protected) sugar stannanes may solve this problem (Scheme 3).
Scheme 3. (i) Swern oxidation; (ii) Ph3PCHCO2Me, CH2Cl2; (iii) (1) DIBAL-H; (2) NaH, THF, CS2, then MeI; (3) toluene, 110 C, 2 h; (4) Bu3SnH, AIBN, toluene, re¯ux; (iv) ZnCl2; (v) NaBH4
Methyl 2,3-di-O-benzyl-b-d-ribofuranoside11 30 was converted into unsaturated ester 31 as a ca. 4:1 mixture of E:Z-isomers and then into allyltin derivative 32 according to a method shown in Scheme 2. Treatment of the latter with a Lewis acid induced a rearrangement with elimination of tri-nbutyltin moiety and formation of the aldehyde 34, which was characterized further as alcohol 35. 3. Conclusion The synthesis of dierently substituted chiral, highly oxygenated dienes was realized by a mild Lewis acid induced, controlled decomposition of sugar allyltins. This procedure gives monosubstituted dienes with the trans-con®guration of the internal double bond exclusively. The convenient synthesis of unsaturated a-hydroxyaldehydes can also be realized by this methodology. 4. Experimental 4.1. General NMR spectra were recorded with a Varian Gemini 200 spectrometer for solutions in CDCl3 (internal Me4Si). Mass spectra [LSIMS (m-nitrobenzyl alcohol was used as a matrix to which
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sodium acetate was added) or EI] were recorded with an AMD-604 (AMD Intectra GmbH, Germany) mass spectrometer. Speci®c rotations were measured with a JASCO DIP Digital Polarimeter in chloroform solution (c 1) at room temperature. Column chromatography was performed on silica gel (Merck, 70±230 mesh). Organic solutions were dried over anhydrous magnesium or sodium sulfate. 4.2. Preparation of sugar allyltin derivatives The sugar allyltin derivatives were prepared from the corresponding alcohols 5, 14, and 30 according to our previously published methods3 involving (cf. Scheme 1): (i) (ii) (iii) (iv) (v) (vi)
oxidation of a sugar alcohol to an aldehyde; reaction with the stabilized Wittig reagent (to a,b-unsaturated ester); reduction of the ester function with DIBAL-H; formation of a xanthate; its thermal rearrangement into thiocarbonate; reaction with tri-n-butyltin hydride under radical conditions.
The procedure for the preparation of 11 is representative. 4.2.1. Methyl 2,3,5-tri-O-benzyl-6,7,8-trideoxy-8-tributylstannyl- -d-galacto-oct-6-eno-1,4-furanoside 11 To a solution of the Swern reagent12 (prepared from 1 mL of oxalyl chloride and 3 mL of DMSO in 30 mL of CH2Cl2) a solution of alcohol 57 (2.3 g, 5 mmol) in CH2Cl2 (15 mL) was added at ^78 C, and the mixture was stirred for 30 min at this temperature. Triethylamine (4 mL) was added, the mixture was stirred at ^78 C for another 30 min and partitioned between ether (100 mL) and water (30 mL). The organic layer was separated, washed with water, dried and concentrated, and the crude aldehyde 6 was dissolved in benzene (50 mL) containing Ph3PCHCO2Me (2.34 g, 7 mmol). After 16 h at room temperature, the solvent was evaporated in vacuum and the product ester 7 (trans:cis=2.5:1) was isolated by column chromatography (hexane:ethyl acetate, 6:1!3:1); yield 82%. trans-7: 1H NMR : 6.94 (dd, J5,6=5.7, J6,7=15.8, H-6), 6.09 (d, H-7), 4.95 (J1,2=0, H-1), 3.69 (CO2CH3), 3.35 (OCH3); 13C NMR : 166.2 (CO), 144.4 and 123.1 (C-6,7), 107.1 (C-1), 87.7, 82.7, 82.6 and 76.7 (C-2,3,4,5), 72.1, 71.7 and 71.6 (3CH2Ph), 54.9 and 51.6 (OCH3 and CO2CH3); HRMS m/z: 541.2202 [C31H34O7Na (M+Na+) requires 541.2202]. cis-7: 1H NMR : 6.35 (dd, J5,6=8.8, J6,7=11.7, H-6), 5.94 (dd, J5,7=0.87, H-7), 4.98 (d, J1,2=1.1, H-1), 3.67 (CO2CH3), 3.33 (OCH3); 13C NMR : 165.9 (CO), 146.9 and 121.9 (C-6,7), 107.2 (C-1), 87.9, 83.5 and 82.5 (C-2,3,4), 73.2, 72.0 and 71 (3CH2Ph), 54.9 and 51.4 (OCH3 and CO2CH3). To a cooled ^78 C solution of 7 (5 g, 9.7 mmol) in dry methylene chloride a 1 M solution of DIBAL-H in hexane (20 mL, 20 mmol) was added and the mixture was stirred for 2 h at ^78 C. The excess of hydride was decomposed by addition of ethyl acetate (2 mL) and, after warming to room temperature, water (10 mL). Insoluble material was ®ltered o by suction, the ®ltrate was dried, concentrated, and the productÐalcohol 8Ðwas isolated by column chromatography (hexane:ethyl acetate, 4:1!2:1); yield 86%. HRMS m/z: 513.2252 [C31H34O7Na (M+Na+) requires 513.2253].
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(Caution: The next sequence of reactions must be performed in a well-ventilated fume hood). To a solution of alcohol 8 (4.02 g, 8.2 mmol) in dry THF (30 mL) sodium hydride (ca. 60% suspension in mineral oil, 0.5 g) was added followed by a catalytic amount of imidazole (ca. 50 mg). The mixture was stirred at room temperature under an argon atmosphere for 1 h. Carbon disul®de (neat, 1 mL) was added and the mixture was stirred for another 30 min. MeI (1.5 mL) was then added, the mixture was stirred for 2 h at room temperature, and partitioned between ether (50 mL) and brine (20 mL). The organic layer was separated, washed with water, dried, and concentrated. A solution of crude xanthate 9 in dry toluene was purged with argon and heated under re¯ux until TLC (hexane:ethyl acetate, 5:1) indicated disappearance of the starting material and formation of a new slightly less polar product thiocarbonate 10 (2±3 h, two stereoisomers of very similar polarity were seen by TLC). Tri-n-butyltin hydride (2.9 mL, 11 mmol) in toluene (5 mL) was added dropwise over 5 min (caution: reaction is very exothermic), and heating was continued until TLC (hexane:ethyl acetate, 6:1) indicated disappearance of starting material and formation of a new less polar product (ca. 30 min). The solvent was evaporated under vacuum and the product was puri®ed by column chromatography (hexane:diethyl ether, 20:1!9:1) to aord 11 as colorless syrup, yield 53%. Compound 11 (pure trans-isomer). 1H NMR : 5.82 (ddd, J6,7=15.2, J7,8a=8.6, J7,8b=6.7, H-7), 5.34 (dd, J5,6=8.8, H-6), 4.96 (d, J1,2=1, H-1), 3.79 (dd, J4.5=3, H-4), 3.35 (OCH3); 13C NMR : 136.0 and 121.6 (C-6,7), 107.0 (C-1), 88.3, 84.0, 83.3 and 78.7 (C-2,3,4,5), 72.2, 71.7 and 69.4 (3CH2Ph), 54.7 (OCH3), 29.8, 27.3 and 9.9 [3Sn(CH2)3CH3], 14.5 (C-8), 13.7 [Sn(CH2)CH3]; HRMS m/z: 707.2743 [C38H51O120 5 Sn (M^57) requires 707.2759]. 4.2.2. 3,5-Di-O-benzyl-1,2-O-isopropylidene-6,7,8-trideoxy-8-tributylstannyl- -d-gluco-oct-6-eno-1,4furanose 15 This compound was prepared as a 9:1 trans:cis mixture from known 3,5-di-O-benzyl-1,2-Oisopropylidene-a-d-glucofuranose9 according to the above procedure. Overall yield: 45%. MS-EI m/z: [643, M^57]; 1H NMR for trans-15 : 5.98 (ddd, J6,7=15.2, J7,8a=8.0, J7,8b=5.9, H-7), 5.89 (d, J1,2=3.7, H-1), 5.29 (m, H-6), 1.83 (m, H-8a,b), 1.47 and 1.29 [C(CH3)2]; 13C NMR : 136.5 and 123.0 (C-6,7), 111.4 [C(CH3)2], 104.9 (H-1), 82.2, 81.9, 81.7 and 77.6 (C-2,3,4,5), 72.2 and 69.5 (2CH2Ph), 29.1, 27.3 and 13.7 [Sn(CH2)3CH3], 26.7 and 26.3 [C(CH3)2], 14.6 (C-8), 9.2 [Sn(CH2)3CH3]. 4.2.3. 3-O-Benzyl-1,2-O-isopropylidene-5,6,7-trideoxy-7-tributylstannyl- -d -xylo-hept-5-eno-1,4furanose 24 This compound was prepared as a ca. 4:1 mixture of trans:cis-isomers from known 3-O-benzyl1,2-O-isopropylidene-5,6-di-deoxy-a-d-xylo-hept-5(E/Z)-eno-1,4-furanose according to the procedure described in Section 4.2.1. 1 HRMS m/z: 523.1880 [C25H39O120 4 Sn (M^57) requires 523.1870]; H NMR data for the transisomer : 5.99 (m, H-6), 5.85 (d, J1,2=4.0, H-1), 5.45 (m, H-5), 3.71 (J2,3=0, J3,4=2.9, H-3), 1.50 and 1.30 [C(CH3)2]; 13C NMR : 136.9 and 118.2 (C-5,6), 111.0 [C(CH3)2], 104.4 (C-1), 83.9, 82.8 and 82.1 (C-2,3,4), 72.1 (CH2Ph), 29.1, 27.3 and 13.7 [3Sn(CH2)3CH3], 26.7 and 26.1, [C(CH3)2], 14.8 (C-7), 9.3 [Sn(CH2)3CH3]. 4.2.4. Methyl 2,3-di-O-benzyl-5,6,7-trideoxy-7-tributylstannyl- -d-ribo-hept-5-eno-1,4-furanoside 32 This compound was prepared from known11 alcohol 30, via unsaturated ester 31 {ca. 4:1 trans:cis mixture. HRMS m/z: 421.1625 [C23H26O6Na (M+Na+) requires 421.1627]; data for the
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main trans-isomer: 1H NMR : 6.94 (dd, J4,5=5.5, J5,6=15.8, H-5), 6.10 (dd, J4,6=1.5, H-6), 4.92 (J1,2=0, H-1), 3.74 (CO2CH3), 3.36 (OCH3); 13C NMR : 146.6 and 121.2 (CO), 106.4 (C-1), 81.8, 79.8 and 79.5 (C-2,3,4), 72.8 and 72.4 (2CH2Ph), 55.6 and 51.6 (OCH3 and CO2CH3)} according to the procedure described in Section 4.2.1. Compound 32 (only trans). 1H NMR : 5.92 (ddd, J5,6=14.9, J6,7a=8.8, J6,7b=8.5, H-6), 5.21 (dd, J4,5=8.3, H-5), 4.86 (J1,2=0, H-1), 3.34 (OCH3); 13C NMR : 135.2 and 124.4 (C-5,6), 105.6 (C-1), 82.8, 82.3 and 80.1 (C-2,3,4), 72.5 and 72.2 (2CH2Ph), 54.9 (OCH3), 29.1, 27.3 and 9.2 [Sn(CH2)3CH3], 14.6 (C-7), 13.8 [Sn(CH2)3CH3]; HRMS m/z: 667.2789 [C34H52O4Na120Sn (M+Na+) requires 667.2785]. 4.3. Reaction of sugar allyltin derivatives with Lewis acids The corresponding allyltin derivative (11, 15, 17, 24 or 32; 3 mmol each) was dissolved in anhydrous methylene chloride (30 mL). A 2.0 M solution of ZnCl2 etherate in methylene chloride (3 mL, 6 mmol) was added, the mixture was stirred at room temperature for 20 min, and partitioned between ether (50 mL) and brine (30 mL). The organic layer was separated, washed with water, dried and concentrated and the products were isolated by column chromatography (hexane:diethyl ether, 7:1). Dienes 18 and 25 were characterized as acetates. 4.3.1. Methyl 2,3-di-O-benzyl-5,6,7,8-tetradeoxy- -l-arabino-oct-5(E),7-dieno-1,4-furanoside 12 1 H NMR : 6.33 (m, H-6,7), 5.72 (dd, J4,5=7.8, J5,6=14.1, H-5), 5.19 (m, both H-8), 4.91 (d, J1,2=1.3, H-1), 4.44 (m, J3,4=7.1, H-4), 4.00 (dd, J2,3=3.5, H-2), 3.78 (dd, H-3), 3.37 (OCH3); 13 C NMR : 136.0, 133.8 and 130.8 (C-5,6,7), 118.4 (C-8), 88.6, 87.5 and 81.3 (C-2,3,4), 72.3 and 72.0 (2CH2Ph), 54.8 (OCH3); HRMS m/z: 389.1752 [C23H26O4Na (M+Na+) requires 389.1729]. 4.3.2. 3-O-Benzyl-1,2-O-isopropylidene-5,6,7,8-tetradeoxy- -d-xylo-oct-5(E),7-dieno-1,4-furanose8 13 When this compound was prepared by controlled decomposition of allyltin 15 only the transisomer was detected in the NMR spectra. 1 H NMR : 6.36 (m, H-6,7), 5.95 (d, J1,2=3.8, H-1), 5.85 (dd, J4,5=7.5, J5,6=14.8, H-5), 5.20 (m, both H-8), 3.85 (dd, J3,4=3.1, H-3), 1.50 and 1.31 [C(CH3)2]; 13C NMR : 136.1, 134.6, 127.1 (C-5,6,7), 118.2 (C-8), 111.4 [C(CH3)2], 104.7 (C-1), 83.4, 82.9, 80.8 (C-2,3,4), 72.0 (CH2Ph), 26.7, 26.1 [C(CH3)2]. When this product was obtained according to Narkunan and Nagarajan8 (see also Scheme 1) additional signals, that could be connected with the cis-isomer, were seen in the 13C NMR spectrum at : 133.0, 131.7, 125.0 (C-5,6,7), 119.8 (C-8), and 112.1 [C(CH3)2]. Also, in the 1H NMR spectrum the H-3 resonance split into two signals at : 3.89 (the minor cis-isomer) and 3.85 (the main trans-isomer). Integration of these signals allowed us to estimate the trans:cis ratio at 9:1. 4.3.3. 1-O-Acetyl-3-O-benzyl-1,2-O-isopropylidene-4,5,6,7-tetradeoxy-4(E),6-dieno-d-erythro-heptose 18-Ac 1 H NMR : 6.36 (m, H-5,6), 6.22 (d, J1,2=2.3, H-1), 5.65 (dd, J3,4=7.7, J4,5=14.5, H-4), 5.21 (m, H-7), 4.23 (dd, J2,3=6.2, H-2), 3.87 (dd, H-3), 2.07 (COCH3), 1.47 and 1.46 [C(CH3)2]; 13C NMR : 170.1 (CO), 135.9, 135.8 and 129.0 (C-4,5,6), 118.7 (C-7), 112.9 [C(CH3)2], 96.6 (C-1), 83.6 and 78.8 (C-2,3), 70.5 (CH2Ph), 27.2 and 26.7 [C(CH3)2], 21.2 (COCH3).
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4.3.4. 1-O-Acetyl-3-O-benzyl-1,2-O-isopropylidene-4,5,6,7-tetradeoxy-4(E),6-dieno-d-threo-heptose 25-Ac 1 H NMR : 6.34 (m, H-5,6), 6.17 (d, J1,2=2.3, H-1), 5.63 (dd, J3,4=8.2, J4,5=14.6, H-4), 5.20 (m, both H-7), 4.30 (dd, J2,3=5.5, H-2), 3.95 (dd, H-3), 2.06 (COCH3), 1.48 and 1.44 [C(CH3)2]; 13 C NMR : 170.2 (CO), 136.2, 135.5 and 128.7 (C-4,5,6), 118.9 (C-7), 113.1 [C(CH3)2], 96.4 (C-1), 83.8 and 78.3 (C-2,3), 70.2 (CH2Ph), 27.0 and 26.9 [C(CH3)2], 21.2 (COCH3); HRMS m/z: 355.1521 [C19H24O5Na (M+Na+) requires 355.1521]. 4.4. Basic hydrolysis of dioxolanes 18 and 25 To a solution of 18 or 25 (3 mmol) in benzene (30 mL), triethylamine (1 mL), methanol (1 mL) and water (1 mL) were added and the mixture was stirred at room temperature for 3 h. Toluene (20 mL) was added, and the solution was concentrated to ca. half volume, dried and concentrated to give in almost quantitative yield 2(R)-hydroxy-3(R)-benzyloxy-hepta-4(E),6-dienal 19 and 2(R)hydroxy-3(S)-benzyloxy-hepta-4(E),6-dienal 26. These hydroxyaldehydes were rather unstable and should be prepared directly before use in the next step. 4.5. Reaction of hydroxyaldehydes with the stabilized Wittig reagent Freshly prepared aldehyde (19 or 26; 1 mmol) was dissolved in dry benzene (10 mL) to which Ph3PCH±CO2Me (0.5 g, 1.5 mmol) was added. The mixture was stirred for 3 h at room temperature, concentrated, and the product was isolated by column chromatography (hexane:ethyl acetate, 6:1). 4.5.1. Methyl 4(R)-hydroxy-5(R)-benzyloxy-nona-2(E),6(E),8-trienoate 21 [ ]D ^87.7. 1H NMR : 6.95 (dd, J2,3=15.8, J3,4=4.6, H-3), 6.33 (m, H-7,8), 6.11 (dd, J2,4=1.7, H-2), 5.62 (dd, J5,6=8.1, J6,7=14.5, H-6), 5.22 (m, both H-9), 4.36 (H-4), 3.93 (dd, J4,5=4.4, H-5), 3.72 (CO2CH3); 13C NMR : 166.7 (CO), 145.7 and 121.6 (C-2,3), 136.2, 135.7 and 128.7 (C-6,7,8), 118.9 (C-9), 81.6 (C-5), 72.9 (C-4), 70.4 (CH2Ph), 51.5 (CO2CH3); HRMS m/z: 311.1280 [C17H20O4Na (M+Na+) requires 311.1259]. 4.5.2. Methyl 4(R)-hydroxy-5(S)-benzyloxy-nona-2(E),6(E),8-trienoate 27 [ ]D +116.0. 1H NMR : 6.89 (dd, J2,3=15.6, J3,4=4.2, H-3), 6.36 (m, H-7,8), 6.16 (dd, J2,4=1.9, H-2), 5.61 (dd, J5,6=8.4, J6,7=14.3, H-6), 5.24 (m, both H-9), 4.27 (m, H-4), 3.73 (H-5, CO2CH3); 13C NMR : 166.7 (CO), 145.6 and 121.6 (C-2,3), 136.6, 135.6 and 128.8 (C-6,7,8), 119.3 (C-9), 82.2 (C-5), 73.1 (C-4), 70.4 (CH2Ph), 51.6 (CO2CH3); HRMS m/z: 311.1289 [C17H20O4Na (M+Na+) requires 311.1259]. 4.6. Reduction of hydroxyaldehydes 19, 26 and alkoxyaldehyde 34 Freshly prepared aldehyde 19 or 26 (1 mmol; obtained by hydrolysis of the corresponding dioxolanes, 18 and 25) or 34 (obtained by the controlled decomposition of 1 mmol of allyltin 32 according to Section 4.3) was dissolved in a THF:methanol mixture (1:1 v/v, 20 mL), to which sodium borohydride (0.1 g) was added. The mixture was stirred for 1 h, concentrated, then the product was extracted with ether, acetylated under standard conditions and puri®ed by column chromatography (hexane:ethyl acetate, 2:1).
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4.6.1. 1,2(R)-Di-acetoxy-3(R)-benzyloxy-hepta-4(E),6-diene 20-Ac [ ]D ^88.9. 1H NMR : 6.33 (m, H-5,6), 5.60 (dd, J3,4=8.1, J4,5=14.3, H-4), 5.20 (m, H-2, both H-7), 3.96 (dd, J2,3=6.2, H-3), 2.01 and 1.99 (2COCH3); 13C NMR : 170.5 and 170.0 (2CO), 135.7, 135.6 and 129.3 (C-4,5,6), 118.7 (C-7), 77.6 and 72.4 (C-2,3), 70.3 (CH2Ph), 62.4 (C-1), 20.8 and 20.7 (2COCH3); HRMS m/z: 341.1362 [C18H22O5Na (M+Na+) requires 341.1365]. 4.6.2. 1,2(R)-Di-acetoxy-3(S)-benzyloxy-hepta-4(E),6-diene 28-Ac [ ]D +26.6. 1H NMR : 6.34 (m, H-5,6), 5.59 (dd, J3,4=7.8, J4,5=14.5, H-4), 5.22 (m, H-2, both H-7), 4.31 and 4.10 (2dd, J1a,1b=11.8, J1a,2=3.7, J1b,2=7.0, both H-1), 4.01 (dd, J2,3=5.3, H-3), 2.08 and 1.99 (2COCH3); 13C NMR : 170.5 and 170.2 (2CO), 135.7, 135.5 and 128 (C-4,5,6), 118.9 (C-7), 77.2 and 72.5 (C-2,3), 70.4 (CH2Ph), 62.8 (C-1), 20.9 and 20.7 (2COCH3); HRMS m/z: 341.1350 [C18H22O5Na (M+Na+) requires 341.1365]. 4.6.3. 1-Acetoxy-2(R),3(S)-di-benzyloxy-hepta-4(E),6-diene 35-Ac 1 H NMR : 6.35 (m, H-5,6), 5.68 (dd, J3,4=8.1, J4,5=14.5, H-4), 5.21 (m, both H-7), 4.32 (dd, J1a,1b=11.8, J1a,2=3.7, H-1a), 4.19 (dd, J1b,2=5.7, H-1b), 3.95 (dd, J2,3=5.7, H-3), 3.68 (m, H-2), 1.98 (COCH3); 13C NMR : 170.8 (CO), 136.0, 135.2 and 130.6 (C-4,5,6), 118.1 (C-7), 79.0 and 78.8 (C-2,3), 72.8 and 70.4 (2CH2Ph), 63.4 (C-1), 20.9 (COCH3); HRMS m/z: 389.1725 [C23H26O4Na (M+Na+) requires 389.1729]. 4.7. Synthesis of dienes 22 and 29 Diol 20 or 28 (1 mmol) was dissolved in ether (20 mL) and added to a solution of sodium periodate (0.7 g) in water (10 mL). The heterogeneous mixture was stirred for 30 min, the organic layer was separated, dried and concentrated, and the crude aldehyde was reduced with sodium borohydride as described in Section 4.6. For better characterization, products alcohols 22 and 29 were acetylated and these derivatives were puri®ed by column chromatography (hexane:ethyl acetate, 4:1) 4.7.1. 1-Acetoxy-2(R)-benzyloxy-hexa-3(E),5-diene 22-Ac [ ]D ^87.9. 1H NMR : 6.35 (m, H-4,5), 5.61 (dd, J2,3=6.8, J3,4=14.3, H-3), 5.19 (m, both H6), 4.11 (m, H-2, both H-1), 2.05 (COCH3); 13C NMR : 170.8 (CO), 135.8, 134.8 and 129.6 (C3,4,4), 118.6 (C-6), 76.9 (C-2), 70.4 (CH2Ph), 66.2 (C-1), 20.8 (COCH3); HRMS m/z: 269.1165 [C15H18O3Na (M+Na+) requires 269.1154]. 4.7.2. 1-Acetoxy-2(S)-benzyloxy-hexa-3(E),5-diene 29-Ac (=ent-22-Ac) [ ]D +85.5. HRMS m/z: 269.1153 [C15H18O3Na (M+Na+) requires 269.1154]. The NMR spectra of this compound were identical in all respects with the spectra of 22-Ac. References 1. Pindur, U.; Lutz, G.; Otto, Ch. Chem. Rev. 1993, 93, 741±761. 2. See, for example: Guliano, R. M.; Buzby, J. H.; Marcopulos, M.; Dpringor, J. P. J. Org. Chem. 1990, 55, 3555± 3562, and references cited therein; Lopez, J. C., Lameignere, E.; Burnouf, C.; Laborde, M. A.; Ghini, A. A.; Olesker, A.; Lukacs, G. Tetrahedron 1993, 49, 7701±7722; Gomez, A. M.; Lopez, J. C.; Fraser-Reid, B. Synthesis
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3. 4. 5. 6. 7. 8.
9. 10. 11. 12.
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1993, 943±944; Lopez, J. C.; Gomez, A. M.; Fraser-Reid, B. J. Chem. Soc., Chem. Commun. 1993, 762±764; Roman, E.; Banos, M.; Higes, F. J.; Serrano, J. A. Tetrahedron: Asymmetry 1998, 9, 449±458, and references cited therein. Kozowska, E.; Jarosz, S. Carbohydr. Res. 1994, 13, 889±898. . Jarosz, S.; Kozowska, E.; Jezewski, A. Tetrahedron 1997, 53, 10 775±10 282; Jarosz, S.; SkoÂra, S. Tetrahedron: Asymmetry 2000, 11, 1425±1432. Jarosz, S. J. Chem. Soc., Perkin Trans. 1 1997, 3579±3580; Jarosz, S.; SkoÂra, S. Tetrahedron: Asymmetry 2000, 11, 1433±1448. Ref. 3; see also Jarosz, S. Tetrahedron 1997, 53, 10 765±10 774. Veeneman, G. H.; Notermans, S.; Hoogerhout, P.; van Boom, J. H. Recl. Trav. Chim. Pays-Bass 1989, 108, 344± 350. This compound was prepared previously from aldehyde 16 by a two-step procedure involving: (i) reaction with Ph3PCH±CHO; and next with (ii) Ph3PCH2 (Narkunan, K.; Nagarajan, M. J. Chem. Soc., Chem. Commun. 1994, 1705±1706). Although this sequence was reported to be highly selective, we obtained a 9:1 mixture of the trans:cis-isomers because of the lack of selectivity in the ®rst step. Eby, R.; Schuerch, C. Carbohydr. Res. 1982, 100, c41±c43; Stepowska, H.; Zamojski, A. Carbohydr. Res. 1994, 265, 133±138. Brimacombe, J. S.; Kabir, A. K. M. S. Carbohydr. Res. 1986, 150, 35±51; Kawahata, Y.; Takatsuto, S.; Ikekawa, N.; Murat, M.; Omura, S. Chem. Pharm. Bull. 1986, 34, 3102±3110. Mereyala, H. B.; Gurrala, S. R. Chem. Lett. 1998, 863±864. Mancuso, A. J.; Huang, S.-L.; Swern, D. J. Org. Chem. 1978, 43, 2480±2482.